Bottom Line:
We find, e.g. that the solution structure of synthetic oligomers is characterized by 100-200 A coherence length, which is similar to approximately 150 A coherence length of natural, salmon-sperm DNA.Packing of oligomers in crystals dramatically alters their helical coherence.The coherence length increases to 800-1200 A, consistent with its theoretically predicted role in interactions between DNA at close separations.

ABSTRACTThe twist, rise, slide, shift, tilt and roll between adjoining base pairs in DNA depend on the identity of the bases. The resulting dependence of the double helix conformation on the nucleotide sequence is important for DNA recognition by proteins, packaging and maintenance of genetic material, and other interactions involving DNA. This dependence, however, is obscured by poorly understood variations in the stacking geometry of the same adjoining base pairs within different sequence contexts. In this article, we approach the problem of sequence-dependent DNA conformation by statistical analysis of X-ray and NMR structures of DNA oligomers. We evaluate the corresponding helical coherence length--a cumulative parameter quantifying sequence-dependent deviations from the ideal double helix geometry. We find, e.g. that the solution structure of synthetic oligomers is characterized by 100-200 A coherence length, which is similar to approximately 150 A coherence length of natural, salmon-sperm DNA. Packing of oligomers in crystals dramatically alters their helical coherence. The coherence length increases to 800-1200 A, consistent with its theoretically predicted role in interactions between DNA at close separations.

Figure 2: Statistical analysis of twist and rise for different possible base pair steps in the standard reference frame (local z/3DNA). Squares show the values for 22 selected straight oligomers with known X-ray structures, circles show the values for 26 selected straight oligomers with known NMR structures, and diamonds show the average twist values reported in (32) based on electrophoretic measurements. The error bars show standard deviations based on measurements of the same step parameters within different contexts. Note that the same base pair step may be denoted, e.g. AG (5′-A to 3′-G) based on one strand or CT (5′-C to 3′-T) based on the complementary strand. Both possible notations for such steps are shown, separated by a slash.

Mentions:
To characterize sequence effects in the double helix structure, we generated DNA-cry models based on known X-ray crystal structures of different oligomers with no visible defects, nucleotide modifications and co-crystallized macromolecules (see ‘Methods’ section). We built separate models based on a full set of 50 such oligonucleotide structures and its different subsets, all of which produced similar results discussed in Supplementary material. Here we show the results obtained for a subset of 22 oligonucleotides with no kinks or bending apparent upon examination with a 3D viewer. We similarly generated DNA-nmr models based on known NMR solution structures of 26 oligomers, also with no defects, apparent kinks or bending. The NDB names and nucleotide sequences of all oligomers are listed in the Supplementary material. The average values of the twist and rise and their dispersions for different base pair steps in these oligomers (Figure 2) were consistent with the corresponding values reported (32,43) from less selective data sets (see Figure S1A and C in the Supplementary material).Figure 2.

Figure 2: Statistical analysis of twist and rise for different possible base pair steps in the standard reference frame (local z/3DNA). Squares show the values for 22 selected straight oligomers with known X-ray structures, circles show the values for 26 selected straight oligomers with known NMR structures, and diamonds show the average twist values reported in (32) based on electrophoretic measurements. The error bars show standard deviations based on measurements of the same step parameters within different contexts. Note that the same base pair step may be denoted, e.g. AG (5′-A to 3′-G) based on one strand or CT (5′-C to 3′-T) based on the complementary strand. Both possible notations for such steps are shown, separated by a slash.

Mentions:
To characterize sequence effects in the double helix structure, we generated DNA-cry models based on known X-ray crystal structures of different oligomers with no visible defects, nucleotide modifications and co-crystallized macromolecules (see ‘Methods’ section). We built separate models based on a full set of 50 such oligonucleotide structures and its different subsets, all of which produced similar results discussed in Supplementary material. Here we show the results obtained for a subset of 22 oligonucleotides with no kinks or bending apparent upon examination with a 3D viewer. We similarly generated DNA-nmr models based on known NMR solution structures of 26 oligomers, also with no defects, apparent kinks or bending. The NDB names and nucleotide sequences of all oligomers are listed in the Supplementary material. The average values of the twist and rise and their dispersions for different base pair steps in these oligomers (Figure 2) were consistent with the corresponding values reported (32,43) from less selective data sets (see Figure S1A and C in the Supplementary material).Figure 2.

Bottom Line:
We find, e.g. that the solution structure of synthetic oligomers is characterized by 100-200 A coherence length, which is similar to approximately 150 A coherence length of natural, salmon-sperm DNA.Packing of oligomers in crystals dramatically alters their helical coherence.The coherence length increases to 800-1200 A, consistent with its theoretically predicted role in interactions between DNA at close separations.

ABSTRACTThe twist, rise, slide, shift, tilt and roll between adjoining base pairs in DNA depend on the identity of the bases. The resulting dependence of the double helix conformation on the nucleotide sequence is important for DNA recognition by proteins, packaging and maintenance of genetic material, and other interactions involving DNA. This dependence, however, is obscured by poorly understood variations in the stacking geometry of the same adjoining base pairs within different sequence contexts. In this article, we approach the problem of sequence-dependent DNA conformation by statistical analysis of X-ray and NMR structures of DNA oligomers. We evaluate the corresponding helical coherence length--a cumulative parameter quantifying sequence-dependent deviations from the ideal double helix geometry. We find, e.g. that the solution structure of synthetic oligomers is characterized by 100-200 A coherence length, which is similar to approximately 150 A coherence length of natural, salmon-sperm DNA. Packing of oligomers in crystals dramatically alters their helical coherence. The coherence length increases to 800-1200 A, consistent with its theoretically predicted role in interactions between DNA at close separations.